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Dexamethasone phosphate-loaded folate-conjugated polymeric nanoparticles for selective delivery to activated macrophages and suppression of inflammatory responses

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Abstract

Activated macrophages play a central role in the pathology of inflammatory diseases by secreting pro-inflammatory cytokines. In this study, we have developed folate-conjugated dexamethasone phosphate (DP)-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) that can selectively target to activated macrophages for alleviation of inflammatory responses. DP was loaded into PLGA nanoparticles in an amorphous form using an ionic interaction between DP, zinc, and PLGA. Folic acid (FA) was used as a targeting ligand for activated macrophages and conjugated onto DPNPs (FA-DPNPs). The mean particle size of DPNPs and FA-DPNPs was 126±36 and 133±28 nm, respectively. The zeta potential of DPNPs and FA-DPNPs were −13.5±0.4 mV and −14.9±0.9 mV, respectively. Sustained and controlled DP release over 48 hours from DPNPs and FA-DPNPs was observed. The low cellular uptake of both DPNPs and FA-DPNPs was observed in normal RAW264.7 macrophages, whereas significantly higher cellular uptake of FA-DPNPs was observed as compared to DPNPs in activated RAW264.7 macrophages. The production of pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO) from activated macrophages was inhibited more significantly by FA-DPNPs than by free DP and DPNPs. Taken together, DP-loaded nanoparticles, especially when conjugated with FA, were selectively internalized by activated macrophages and effectively suppressed inflammatory responses. DP loaded folate-conjugated PLGA nanoparticles presented in this study may offer a promising approach of targeted delivery to activated macrophages for the treatment of inflammatory diseases.

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References

  1. D. L. Laskin and K. J. Pendino, Annu. Rev. Pharmacol. Toxicol., 35, 655 (1995).

    Article  CAS  Google Scholar 

  2. Y. D. Park, C. H. Jin, D. S. Choi, M.-W. Byun, and I. Y. Jeong, Arch. Pharm. Res., 34, 1277 (2011).

    Article  CAS  Google Scholar 

  3. H. Hasturk, A. Kantarci, and T. E. Van Dyke, Front. Immunol., 3, 118 (2012).

    Article  Google Scholar 

  4. D. Hristodorov, R. Mladenov, M. Huhn, S. Barth, and T. Thepen, Toxins, 4, 676 (2012).

    Article  CAS  Google Scholar 

  5. F. O. Martinez and S. Gordon, F1000Prime Rep., 6 (2014).

    Google Scholar 

  6. T. Lawrence, D. W. Gilroy, P. R. Colville-Nash, and D. A. Willoughby, Nat. Med., 7, 1291 (2001).

    Article  CAS  Google Scholar 

  7. T. A. Wynn, A. Chawla, and J. W. Pollard, Nature, 496, 445 (2013).

    Article  CAS  Google Scholar 

  8. P. J. Barnes, Clin. Sci., 94, 557 (1998).

    CAS  Google Scholar 

  9. W. Hofkens, G. Storm, W. van den Berg, and P. van Lent, Ann. Rheum. Dis., 70, A40 (2011).

    Article  Google Scholar 

  10. P. J. Barnes, Immunol. Allerg. Clin. North Am., 25, 451 (2005).

    Article  Google Scholar 

  11. K. G. Saag, Curr. Rheumatol. Rep., 4, 218 (2002).

    Article  Google Scholar 

  12. Y. Malam, M. Loizidou, and A. M. Seifalian, Trends Pharmacol. Sci., 30, 592 (2009).

    Article  CAS  Google Scholar 

  13. T. Ishihara, T. Kubota, T. Choi, and M. Higaki, J. Pharmacol. Exp. Ther., 329, 412 (2009).

    Article  CAS  Google Scholar 

  14. B. Crielaard, T. Lammers, M. Morgan, L. Chaabane, S. Carboni, B. Greco, P. Zaratin, A. Kraneveld, and G. Storm, Int. J. Pharm., 416, 499 (2011).

    Article  CAS  Google Scholar 

  15. J. M. Metselaar, M. H. Wauben, J. Wagenaar-Hilbers, O. C. Boerman, and G. Storm, Arthritis Care Res., 48, 2059 (2003).

    Article  CAS  Google Scholar 

  16. J. Hwang, K. Rodgers, J. C. Oliver, and T. Schluep, Int. J. Nanomed., 3, 359 (2008).

    CAS  Google Scholar 

  17. P. S. Low and A. C. Antony, Adv. Drug Deliv. Rev., 56, 1055 (2004).

    Article  CAS  Google Scholar 

  18. C. M. Paulos, B. Varghese, W. R. Widmer, G. J. Breur, E. Vlashi, and P. S. Low, Arthritis Res. Ther., 8, R77 (2006).

    Article  Google Scholar 

  19. C. Müller and R. Schibli, Front. Oncol., 3 (2013).

    Google Scholar 

  20. C. M. Paulos, M. J. Turk, G. J. Breur, and P. S. Low, Adv. Drug Deliv. Rev., 56, 1205 (2004).

    Article  CAS  Google Scholar 

  21. J.-S. Choi, K. Seo, and J.-W. Yoo, J. Pharm. Investig., 42, 155 (2012).

    Article  CAS  Google Scholar 

  22. T. Ishihara, M. Takahashi, M. Higaki, and Y. Mizushima, Int. J. Pharm., 365, 200 (2009).

    Article  CAS  Google Scholar 

  23. B. Stella, S. Arpicco, M. T. Peracchia, D. Desmaële, J. Hoebeke, M. Renoir, J. D'Angelo, L. Cattel, and P. Couvreur, J. Pharm. Sci., 89, 1452 (2000).

    Article  CAS  Google Scholar 

  24. P. Katakam and K. R. Sireesha, J. Chem., 9, 1077 (2012).

    CAS  Google Scholar 

  25. C. Gómez-Gaete, N. Tsapis, M. Besnard, A. Bochot, and E. Fattal, Int. J. Pharm., 331, 153 (2007).

    Article  Google Scholar 

  26. M. E. Keegan, J. L. Falcone, T. C. Leung, and W. M. Saltzman, Macromolecules, 37, 9779 (2004).

    Article  CAS  Google Scholar 

  27. D. Kozak, W. Anderson, R. Vogel, S. Chen, F. Antaw, and M. Trau, ACS Nano, 6, 6990 (2012).

    Article  CAS  Google Scholar 

  28. T. Musumeci, C. A. Ventura, I. Giannone, B. Ruozi, L. Montenegro, R. Pignatello, and G. Puglisi, Int. J. Pharm., 325, 172 (2006).

    Article  CAS  Google Scholar 

  29. U. Bhardwaj and D. J. Burgess, Int. J. Pharm., 388, 181 (2010).

    Article  CAS  Google Scholar 

  30. D. H. Kim, J. H. Chung, J. S. Yoon, Y. M. Ha, S. Bae, E. K. Lee, K. J. Jung, M. S. Kim, Y. J. Kim, and M. K. Kim, J. Ginseng Res., 37, 54 (2013).

    Article  CAS  Google Scholar 

  31. D. Feng, W.-H. Ling, and R.-D. Duan, Inflamm. Res., 59, 115 (2010).

    Article  CAS  Google Scholar 

  32. Y. Tabata and Y. Ikada, Biomaterials, 9, 356 (1988).

    Article  CAS  Google Scholar 

  33. J. A. Champion, A. Walker, and S. Mitragotri, Pharm. Res., 25, 1815 (2008).

    Article  CAS  Google Scholar 

  34. J.-S. Choi, J. Cao, M. Naeem, J. Noh, N. Hasan, H.-K. Choi, and J.-W. Yoo, Colloid Surf. B: Biointerfaces, 122, 545 (2014).

    Article  CAS  Google Scholar 

  35. S. Bamrungsap, Z. Zhao, T. Chen, L. Wang, C. Li, T. Fu, and W. Tan, Nanomedicine, 7, 1253 (2012).

    Article  CAS  Google Scholar 

  36. T. Guzik, R. Korbut, and T. Adamek-Guzik, J. Physiol. Pharmacol., 54, 469 (2003).

    CAS  Google Scholar 

  37. K. Ishihara and T. Hirano, Cytokine Growth Factor Rev., 13, 357 (2002).

    Article  CAS  Google Scholar 

  38. F. H. Epstein, C. Gabay, and I. Kushner, N. Engl. J. Med., 340, 448 (1999).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy, Pusan National University, Busan, 609-735, Korea

    Jiafu Cao, Muhammad Naeem, Jin-Ki Noh & Jin-Wook Yoo

  2. College of Pharmacy, Korea University, Sejong, 339-700, Korea

    Eun Hee Lee

Authors
  1. Jiafu Cao
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  2. Muhammad Naeem
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  3. Jin-Ki Noh
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  4. Eun Hee Lee
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  5. Jin-Wook Yoo
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Correspondence to Jin-Wook Yoo.

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Cao, J., Naeem, M., Noh, JK. et al. Dexamethasone phosphate-loaded folate-conjugated polymeric nanoparticles for selective delivery to activated macrophages and suppression of inflammatory responses. Macromol. Res. 23, 485–492 (2015). https://doi.org/10.1007/s13233-015-3065-6

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  • DOI: https://doi.org/10.1007/s13233-015-3065-6

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